Immunogenicity of subcutaneous TNF inhibitors and its clinical significance in real-life setting in patients with spondyloarthritis.

KEY MESSAGES: Considerable proportion of patients with SpA have been immunized to the subcutaneous anti-TNF drug they are using. Concomitant use of MTX protects from immunization, whereas SASP does not. Patients with SpA using subcutaneous anti-TNF drugs can benefit from monitoring of the drug trough levels. Immunization to biological drugs can lead to decreased efficacy and increased risk of adverse effects. The objective of this cross-sectional study was to assess the extent and significance of immunization to subcutaneous tumor necrosis factor (TNF) inhibitors in axial spondyloarthritis (axSpA) patients in real-life setting. A serum sample was taken 1-2 days before the next drug injection. Drug trough concentrations, anti-drug antibodies (ADAb) and TNF-blocking capacity were measured in 273 patients with axSpA using subcutaneous anti-TNF drugs. The clinical activity of SpA was assessed using the Bath AS Disease Activity Index (BASDAI) and the Maastricht AS Entheses Score (MASES). ADAb were found in 11% of the 273 patients: in 21/99 (21%) of patients who used adalimumab, in 0/83 (0%) of those who used etanercept, in 2/79 (3%) of those who used golimumab and in 6/12 (50%) of those who used certolizumab pegol. Use of methotrexate reduced the risk of formation of ADAb, whereas sulfasalazine did not. Presence of ADAb resulted in decreased drug concentration and reduced TNF-blocking capacity. However, low levels of ADAb had no effect on TNF-blocking capacity and did not correlate with disease activity. The drug trough levels were below the consensus target level in 36% of the patients. High BMI correlated with low drug trough concentration. Patients with low drug trough levels had higher disease activity. The presence of anti-drug antibodies was associated with reduced drug trough levels, and the patients with low drug trough levels had higher disease activity. The drug trough levels were below target level in significant proportion of patients and, thus, measuring the drug concentration and ADAb could help to optimize the treatment in SpA patients.

Minor effect of loss to follow-up on outcome interpretation in the Swedish spine register.

BACKGROUND AND PURPOSE: Loss to follow-up in observational studies may skew results and hamper study reliability. We evaluated the importance of loss to follow-up in the Swedish spine register. PATIENTS: Patients operated in the lumbar spine and scheduled for a postal questionnaire follow-up during part of 2016 were identified. Out of the 351 patients, 203 had responded. After multiple attempts, 115 of the 148 non-responders were reached; 68 returned the complete questionnaire; and 47 answered a brief questionnaire by phone. Analyses were made with the Chi-square test, analysis of covariance or logistic regression. Some analyses were adjusted. RESULTS: At baseline, the non-responders were younger than the responders (55 vs 61 years, p < 0.001) and had higher Oswestry Disability Index (ODI) (54 vs 48, p = 0.003), lower SF-36 physical component summary score (PCS) (36 vs 40, p = 0.011) and lower EQ-5D (0.17 vs 0.27, p = 0.018). Mean back pain, leg pain, ODI, EQ-5D, SF-36 mental component summary score (MCS) improved significantly in both groups (all p < 0.001). SF-36 PCS did not improve in the non-responder group (p = 0.063). Non-responders perceived less improvement in back pain (global assessment back 60% vs 72%, p = 0.002). At follow-up, there were no differences in patient-reported outcome measures between the groups (all p ≥ 0.06), with the exception of a lower SF-36 MCS among the non-responders (p = 0.015). INTERPRETATION: After surgery for lumbar spine degenerative disorders, non-responders achieve similar outcome as responders in the Swedish spine register, with the exception of a lower mental health and less perceived improvement in back pain. These slides can be retrieved under Electronic Supplementary Material.

Long-term outcome after spinal fusion for isthmic spondylolisthesis in adults.

BACKGROUND CONTEXT: Data on the long-term outcome after fusion for isthmic spondylolisthesis are scarce. PURPOSE: To study patient-reported outcomes and adjacent segment degeneration (ASD) after fusion for isthmic spondylolisthesis and to compare patient-reported outcomes with a control group. STUDY DESIGN/SETTING: A prospective study including a cross-sectional control group. PATIENT SAMPLE: Patients with isthmic spondylolisthesis underwent posterior lumbar interbody fusion (PLIF) (n=86) or posterolateral fusion (PLF) (n=77). Patient-reported outcome data were available for 73 patients in the PLIF group and 71 in the PLF group at a mean of 11 (range 5-16) years after baseline. Seventy-seven patients in the PLIF group and 54 in the PLF group had radiographs at a mean of 14 (range 9-19) years after baseline. One hundred thirty-six randomly selected persons from the population served as controls for the patient-reported outcomes. OUTCOME MEASURES: Patient-reported outcomes include the following: global outcome, Oswestry Disability Index, Disability Rating Index, and Short Form 36. The ASD was determined from radiographs using the University of California Los Angeles (UCLA) grading scale. METHODS: The chi-square test or analysis of covariance (ANCOVA) was used for group comparisons. The ANCOVA was adjusted for follow-up time, smoking, Meyerding slippage grade, teetotaler (yes/no) and, if available, the baseline level of the dependent variable. RESULTS: There were no significant patient-reported outcome differences between the PLIF group and the PLF group. The prevalence of ASD was 42% (32/77) in the PLIF group and 26% (14/54) in the PLF group (p=.98). The patient-reported outcome data indicated lower physical function and more pain in individuals with surgically treated isthmic spondylolisthesis compared to the controls. CONCLUSIONS: PLIF and PLF groups had similar long-term patient-reported and radiological outcomes. Individuals with isthmic spondylolisthesis have lower physical function and more pain several years after surgery when compared to the general population.

Three out of four disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients meet 28-joint Disease Activity Score remission at 12 months: results from the FIN-ERA cohort.

OBJECTIVE: To assess what proportion of patients with disease-modifying anti-rheumatic drug (DMARD)-naïve early rheumatoid arthritis (ERA) reach 28-joint Disease Activity Score (DAS28) remission over 1 year, and remission variability across clinics in Finland. METHOD: Patients with DMARD-naïve newly diagnosed inflammatory arthritis were recruited. The proportion of patients in 28-joint Disease Activity Score with three variables (DAS28-3) remission was compared across sites. Repeated measures were analysed using a mixed models approach with appropriate distribution and link function. RESULTS: In total, 611 patients were recruited at five sites: 67% were female; the mean (sd) age was 57 (16) years; 71% and 68% were positive for rheumatoid factor and anti-cyclic citrullinated peptides, respectively; and 23% had radiographic erosions. A total of 506 (83%) fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for rheumatoid arthritis for further analyses. DAS28-3 remission was met by 68% and 75% at 3 and 12 months, respectively. The clinical site had no effect on remission when adjusted for confounders. At baseline, 68% used methotrexate-based combination therapy, and 31% used triple therapy with methotrexate, hydroxychloroquine, and sulphasalazine (the Fin-RACo regimen). In multivariate analysis, the only independent predictors of DAS28-3 remission at 12 months were lower baseline DAS28-3 and triple therapy as the initial treatment. CONCLUSION: Three out of four DMARD-naïve ERA patients in Finland are in remission during the first year from the diagnosis. High remission rates were achieved for most patients with the use of conventional synthetic DMARDs in combination. Treatment of DMARD-naïve ERA patients with the FIN-RACo regimen is a predictor of DAS28-3 remission in real-life rheumatology settings.

Ultrasonographic findings in metatarsophalangeal and talocrural joints in healthy persons.

The objective of this study was to establish whether healthy persons have effusions detectable by ultrasonography (US) in metatarsophalangeal (MTP) and talocrural (TC) joints. Fifty consecutive healthy persons without symptoms in ankles and feet were studied. Thirty-eight of them were women, and their mean age was 47.4 (range 23-62) years. Eighteen of the 500 MTP joints studied in nine persons and four of the 100 TC joints in three persons showed effusions upon investigation. One person had effusion in five MTP joints, one in four, two in two, and the remaining five in one MTP joint. None of the studied joints yielded pathological findings in Doppler US examination. These results indicate that the detection of effusion by grayscale US in the absence of Doppler US in MTP and TC joints can be found in healthy persons.

The similiarity of facial expressions in response to emotion-inducing films in reared-apart twins.

BACKGROUND: While the role of genetic factors in self-report measures of emotion has been frequently studied, we know little about the degree to which genetic factors influence emotional facial expressions. METHOD: Twenty-eight pairs of monozygotic (MZ) and dizygotic (DZ) twins from the Minnesota Study of Twins Reared Apart were shown three emotion-inducing films and their facial responses recorded. These recordings were blindly scored by trained raters. Ranked correlations between twins were calculated controlling for age and sex. RESULTS: Twin pairs were significantly correlated for facial expressions of general positive emotions, happiness, surprise and anger, but not for general negative emotions, sadness, or disgust or average emotional intensity. MZ pairs (n=18) were more correlated than DZ pairs (n=10) for most but not all emotional expressions. CONCLUSIONS: Since these twin pairs had minimal contact with each other prior to testing, these results support significant genetic effects on the facial display of at least some human emotions in response to standardized stimuli. The small sample size resulted in estimated twin correlations with very wide confidence intervals.

Nucleostemin mRNA is expressed in both normal and malignant renal tissues.

Nucleostemin (NS), a p53-binding protein, has been shown essential for stem and cancer cell proliferation and implicated in oncogenesis. To explore potential contributions of NS to the development of clear cell renal cell carcinomas (ccRCCs), we determined NS expression in ccRCC cell lines, and in paired normal and malignant renal tissues from 31 patients with ccRCC. Nucleostemin mRNA and/or protein expression was observed in all four cell lines and 27 of 31 (87%) tumour specimens. Surprisingly, 16 of 31 (52%) adjacent normal renal samples also expressed NS mRNA and its levels in four of them were comparable with those in paired tumour tissues. Three of the patients had detectable NS mRNA in their normal renal tissues whereas lacked its expression in the matched tumours. Compared to the oncogene c-MYC expression in these same samples, NS expression showed a much less specificity for ccRCC. We further demonstrated that NS mRNA expression was closely associated with cellular proliferation in normal fibroblasts or T lymphocytes and renal cell carcinoma cell lines. Collectively, NS expression widely occurs in normal and malignant renal tissues, and is likely a proliferation marker rather than a unique regulator of cell proliferation and survival in stem and cancer cells.

The autonomic and behavioral profile of emotional dysregulation.

The authors describe a patient with focal brain atrophy and emotional lability characterized by episodes of excessive crying and laughing. The patient was selectively impaired in the production of voluntary complex facial movements and was unable to regulate her emotional behavior and autonomic reactivity. She also displayed increased behavioral and autonomic changes when explicitly trying to suppress her responses to emotional stimuli (compared with when not trying to regulate her responses). This pattern of deficits supports a selective deficit in voluntary emotional control.

The role of chromosome 8p22 deletion for predicting disease progression and pathological staging in prostate cancer.

The natural course of human prostate cancer is highly variable, and we still lack reliable tools to predict the patient's outcome. Recent publications suggest that the deletion of chromosome 8p22 has an important role for tumor progression in prostate cancer. Totally, 97 patients (41 Japanese and 56 Swedish) were studied to detect the status of chromosome 8p22 deletion by the fluorescence in situ hybridization (FISH) technique. Seventy-seven underwent surgery (59 radical prostatectomies or 18 lymph node dissections), and the specimens were prepared by touch biopsy. Fine-needle aspiration biopsies (FNAB) were obtained from another non-operative 20 cases. Disease progression was evaluated in 57 patients with a median follow-up of 59 months. 8p22 deletions were detected in 58 (60 %) of all cases. The frequency of 8p22 deletion did not significantly differ between different preparations of specimens (touch biopsy vs. FNAB) as well as between different races (Japanese vs. Swedish). Cases with more than pT3 tumors had a significantly higher frequency of 8p22 deletion than those with pT2 (p < 0.01). Multivariate analysis demonstrated that 8p22 deletion was the strongest parameter to predict disease progression (hazard ratio = 5.75; p = 0.0001). Studies on chromosomal deletions of 8p22 by the FISH technique may serve as a universal genetic marker to optimize the treatment strategy in patients with prostate cancer.

Invasion of Salmonella into human intestinal epithelial cells is modulated by HLA-B27.

OBJECTIVE: To investigate the influence of the major histocompatibility complex (MHC) class I molecule HLA-B27 on (i) the invasion of Salmonella and Yersinia into human intestinal epithelial cells, (ii) the survival of intracellular Salmonella in these cells, and (iii) the production of certain inflammatory cytokines by the cells after Salmonella infection. METHODS: The human intestinal epithelial cell line Henle-407 was transfected with HLA-B27 DNA. These cells and HLA-B27-negative control cells were infected with Salmonella or Yersinia, and viable intracellular bacteria were determined as colony-forming units. Cytokine production was assayed with ELISA. RESULTS: Salmonella invaded HLA-B27-positive Henle cells in higher numbers than HLA-B27-negative control cells. However, HLA-B27 did not affect the invasion of Yersinia or the survival of the intracellular bacteria in these intestinal epithelial cells. Salmonella infection induced production of interleukin-8 (IL-8), IL-6 and monocyte chemotactic protein 1 (MCP-1) by Henle cells that was not affected by HLA-B27 in a specific way. CONCLUSIONS: These findings suggest that HLA-B27 enhances the invasion of Salmonella into intestinal epithelial cells. The interaction between bacteria and intestinal epithelial cells plays an important role during the early phases of ReA. HLA-B27-linked modulation of Salmonella invasion may lead to an increased load of Salmonella in intestinal tissue and thus increased susceptibility to reactive arthritis.

A new core-biopsy instrument with an end-cut technique provides prostate biopsies with increased tissue yield.

OBJECTIVE: To evaluate the tissue yield of a new core-biopsy needle with an end-cut mechanism when used for transrectal prostate biopsies. PATIENTS AND METHODS: The end-cut instrument has an adjustable stroke length (13, 23 or 33 mm) and an inner and an outer cannula, but no trocar. It was compared with the conventional side-notch needle (Biopty, Bard, Covington, GA, USA) with trocar and fixed stroke length (22 mm). In 60 men, octant biopsies were taken including the apex, mid-medial, mid-lateral and basal positions. At random, the left side of the prostate was biopsied with one of the instruments and the right side with the other. The length and weight of the biopsy specimens were measured. In 40 men, the stroke length of the end-cut instrument was set to 23 mm, and in 20 men it was set to 33 mm. RESULTS: The weight and the weight per length of the biopsies provided by the end-cut instrument with a stroke length of 23 mm were 18.4% and 13.7%, respectively, greater than in the biopsies from the side-notch instrument (P<0.001). In 21.9% of the attempts no tissue was obtained by the end-cut needle, compared with 1.9% with the side-notch needle. With a 33 mm stroke length, the length and weight of the end-cut biopsies were 38.4% and 33.0%, respectively, greater than in biopsies from the side-notch instrument. CONCLUSION: The end-cut instrument provided a greater tissue yield than the side-notch needle, but a significant number of biopsies were lost.

Deletions on chromosome 8p22 may predict disease progression as well as pathological staging in prostate cancer.

PURPOSE: A recent report demonstrated that the deletion of chromosome 8p22 could predict disease progression in stage III (capsular penetrating) prostate cancer. We studied if the status of chromosomal deletions of 8p22 could reflect pathological stage as well as patient prognosis, thereby serving as a diagnostic tool to optimize the treatment strategy in prostate cancer. EXPERIMENTAL DESIGN: A total of 97 patients (41 Japanese and 56 Swedish) were studied by the fluorescence in situ hybridization technique. Seventy-seven patients (23 pT2, 18 pT3, and 36 pN+ tumors) underwent surgery (radical prostatectomy or lymph node dissection). The specimens were prepared by touch biopsy. From another 20 cases, fine-needle aspiration biopsies were obtained. RESULTS: 8p22 deletions were detected in 47 (61%) and 11 (55%) specimens of 77 touch biopsies and 20 fine-needle aspiration biopsies, respectively. No significant difference was found in the frequency of 8p22 deletion between different preparations of specimens, as well as between different races (Japanese versus Swedish). The frequency of 8p22 deletion was statistically higher in patients with pT3 or more than in those with pT2 (P < 0.01). Disease progression was evaluated in 57 patients. The Cox proportional hazards model revealed 8p22 deletion to be the strongest parameter to predict disease progression (hazards ratio = 5.75; P = 0.0001). CONCLUSIONS: Studies on chromosomal deletions of 8p22 by fluorescence in situ hybridization technique may serve as a genetic marker to optimize the treatment strategy in patients with prostate cancer to the optimal treatment.

Questioning questions about symptoms of benign prostatic hyperplasia.

OBJECTIVES: Our aim was to conduct a survey about urinary symptoms and to find out if questioning patients about symptoms is helpful for the GP to make medical decisions concerning prostate problems among middle-aged men. METHODS: Twelve hundred randomly chosen men aged 55--65 years from the general population in north-west Stockholm, Sweden were sent a questionnaire consisting of symptom questions focusing on prostate problems based on the International Prostate Symptom Score (I-PSS). A subset of 120 respondents were asked to answer the same questions again and to participate in a urological examination including urodynamics and ultrasonography. The main outcome measures were the prevalence of urinary symptoms and the relationship between the symptom score and objective measures. RESULTS: A response rate of 86% was obtained in the questionnaire study. Twenty-one per cent of the respondents stated that they had general problems related to urination. Among individual symptoms, post-void dribbling and a weak stream were most common. Among the men examined at the Urological Department, the average prostatic volume was found to be 40 cm(3). Three out of four were assessed to have infravesical obstruction. No correlation between subjective symptoms and objective measurements of either a statistical or clinical significance was found. CONCLUSIONS: Urinary symptoms are common among middle-aged men. Further, an enlarged prostate and/or infravesical obstruction is often found in the ageing man. Information obtained by asking prostate-specific symptom questions cannot, however, serve as the foundation for the GP to find those men whose problems would be solved by actions directed at the prostate.

Induction of innate immune responses by Escherichia coli and purified lipopolysaccharide correlate with organ- and cell-specific expression of Toll-like receptors within the human urinary tract.

Mucosal epithelial linings function as physical barriers against microbes. In addition, they participate in the first line of host defence by production of a variety of proinflammatory mediators when exposed to microbes and microbial agents. Here, we use a human urinary tract infection model to demonstrate that organ- and cell-specific innate responses induced by lipopolysaccharides (LPS) present on Gram-negative bacteria correlates with the expression of Toll-like receptor 4 (TLR4). The presence of TLR4 on human bladder epithelial cells enables them to rapidly respond to bacterial infections in vitro and in vivo. In contrast, TLR4 is not expressed on human proximal tubule cells isolated from the renal cortex, which may explain the cortical localization of bacteria in pyelonephritis. TLR4-negative renal epithelial cells, A498, are non-responsive to purified LPS, however, they respond to viable bacteria via a mannose-sensitive attachment-mediated pathway. To identify LPS components recognised by bladder epithelial cells, a bacterial lipid A mutant and LPS of different chemotypes were tested. Full interleukin 8 induction required hexa-acylated lipid A and was decreased by between 50% and 70% in the presence of O-antigen. Taken together, we propose that multiple independent pathways, which are organ- and cell-specifically expressed, mediate bacterial recognition and determine the outcome of innate responses to infection.

Relatively high risk of treatment failure after prostatectomy: tumour grade, histopathological stage and the preoperative serum PSA level are key prognosticators.

OBJECTIVE: Prostate cancer is the most common malignancy among males in Sweden. Any reduction in morbidity and mortality would require early detection of cases in which curative treatment is achievable. MATERIAL AND METHODS: From 1994 through 1998. 105 patients with clinically localized T1-T2 tumours were subjected to radical prostatectomy at our department. Three patients were lost to follow-up. We obtained clinical information from the patients' medical records and used pathologist reports to characterize the tumours with respect to grade and histopathological stage. We used serum PSA levels as a surrogate end-point, with a level equal to or above 0.6 ng/ml designated as treatment failure. Outcome was examined with respect to tumour grade, histopathological stage and preoperative PSA level. RESULTS: Altogether, 29% of the patients showed PSA failure during follow-up which varied between 2 and 6 years. No mortality due to prostate cancer was recorded during this time period. We found that tumour grade, histopathological staging and as well as the preoperative PSA level correlated with treatment failure (p<0.01). About 80% of the patients with a preoperative PSA <10 ng/ml showed no signs of treatment failure. The corresponding figure for those with PSA above 10 ng/ ml was 55%. The outcome for patients with a PSA between 10-20 did not seem to be better than that for patients with a preoperative PSA >20 ng/ml. CONCLUSION: Our study indicates, that the risk of treatment failure depends strongly on the grade of the tumour and increases when preoperative PSA value is greater than l0 ng/ml.

Chromosome 8 numerical aberration and C-MYC copy number gain in bladder cancer are linked to stage and grade.

Chromosome 8 aberration and c-myc amplification have been suggested as playing important roles in the development of different human cancers. Using fluorescence in situ hybridization (FISH), chromosome 8 polysomy and c-myc amplification can be detected in cells from bladder cancer. We investigated the correlation of chromosome 8 polysomy, c-myc gene alteration and p53 deletion with histopathological parameters. Twenty-four tumors obtained from patients with bladder cancer were analyzed by interphase cytogenetics using FISH with chromosome 8 and 17 centromere probes together with an YAC clone covering the c-myc locus and three cosmid DNA probes covering the p53 locus. Chromosome 8 polysomy was found in 12 tumors. The average copy number of chromosome 8 centromere signals were significantly higher in high grade and stage, cancers. Also the c-myc copy gain and p53 deletion were significantly correlated with grade as well as stage (p<0.05, in both cases). Both polysomy 8 and c-myc copy gain were significantly correlated with p53 deletions (p<0.01) and DNA ploidy (p<0.001). On the contrary there was no significant correlation between c-myc protein over-expression and c-myc gene amplification. These results may indicate that alteration of chromosomal regions on 8q and 17p, including c-myc and p53 genes, may be linked to progression of bladder cancer.

Linkages between facial expressions of anger and transient myocardial ischemia in men with coronary artery disease.

The authors examined whether facial expressions of emotion would predict changes in heart function. One hundred fifteen male patients with coronary artery disease underwent the Type A Structured Interview, during which time measures of transient myocardial ischemia (wall motion abnormality and left ventricular ejection fraction) were obtained. Facial behavior exhibited during the ischemia measurement period was videotaped and later coded by using the Facial Action Coding System (P. Ekman & W. V. Friesen, 1978). Those participants who exhibited ischemia showed significantly more anger expressions and nonenjoyment smiles than nonischemics. Cook-Medley Hostility scores did not vary with ischemic status. The findings have implications for understanding how anger and hostility differentially influence coronary heart disease risk.

Optimizing the therapeutic approach of transurethral alprostadil.

OBJECTIVE: To investigate the efficacy and safety of two different starting doses of transurethral alprostadil (250 microg and 500 microg, MUSE, Vivus Inc., Menlo Park, CA, USA, and Astra Läkemedel AB, Södertälje, Sweden) and the need for dose titration in a general population with erectile dysfunction. PATIENTS AND METHODS: In a 12-week randomized and open multicentre study with parallel groups, 166 patients were randomised to a starting dose of either 250 or 500 microg of MUSE and evaluated for safety. Of these patients, 142 were included in the analysis of efficacy. MUSE marked in four doses (125, 250, 500 and 1000 microg) was supplied and during the trial the dose could be increased or decreased step-wise until a satisfactory response was attained. The efficacy was assessed using the Erection Assessment Scale (EAS), as coitus (by diary) and the International Index of Erectile Function. RESULTS: The lowest dose of MUSE with which the patients achieved at least one EAS score of 4 or 5 was 125 microg for 1% of participants, 250 ++microg for 27%, 500 microg for 32%, 1000 microg for 6%, and finally 1000 microg plus a pubic band for 8%. Thirty-five of the 142 patients (25%) did not report an EAS of 4 or 5. Most patients (> 60%) achieved an EAS of 4 or 5 on the lower doses (125, 250 and 500 microg). Almost all patients who had an EAS score of 4 or 5 also had intercourse. In all, 68% reported sexual intercourse at least once in course of the study. More patients reported penile pain while treated with 500 microg than with 250 microg (P < 0.05) during the first 4 weeks. However, the penile pain was severe in very few men and it was a minor problem. Hypotensive symptoms were reported six times, independently of dose level. The administration of MUSE was generally rated as comfortable. No patients reported urethral stricture, penile fibrosis, or priapism either in the clinic or at home. CONCLUSION: Recommending 500 microg as a starting dose increased the percentage of patients reporting at least one EAS of 4-5, with or without sexual intercourse, from 28% to 60%. No serious dose-related systemic effects were seen. When starting on 500 microg, patients were more likely to find directly the dose that gave sufficient response and treatment satisfaction. We suggest that the appropriate starting dose of MUSE should be 500 microg.

Modification of disease outcome in Salmonella-infected patients by HLA-B27.

OBJECTIVE: To study whether HLA-B27 modifies the outcome of Salmonella infection in vivo. METHODS: The frequency of HLA-B27 was determined in 198 Salmonella-infected patients and 100 healthy controls by immunofluorescence and polymerase chain reaction. The excretion of Salmonella was monitored at monthly intervals. The symptoms of acute infection and possible joint involvement were evaluated using questionnaires. RESULTS: Thirty-eight of 198 Salmonella-infected patients (19.2%) and 13 of 100 healthy controls (13.0%) were HLA-B27 positive. The excretion of Salmonella did not differ significantly between HLA-B27-positive and -negative patients, or for patients with versus those without joint symptoms. As many as 35 patients (17.7%) reported Salmonella-triggered joint symptoms. Three of 14 patients (21.4%) with arthralgia, 5 of 13 patients (38.5%) with probable reactive arthritis (ReA), and 6 of 8 patients (75%) with confirmed ReA were HLA-B27 positive. The duration and severity of joint symptoms directly correlated with HLA-B27 positivity. Women reported Salmonella-induced pain and swelling of joints more frequently than men (P = 0.07 and P = 0.03, respectively). Patients with Salmonella-triggered joint symptoms reported abdominal pain and headache more frequently than patients without joint symptoms (P = 0.05 and P = 0.004, respectively). CONCLUSION: HLA-B27 did not (at least, not strongly) confer susceptibility to Salmonella infection. Salmonella excretion correlated neither with HLA-B27 positivity nor with the occurrence of joint symptoms. Joint symptoms were surprisingly common during or after Salmonella infection. HLA-B27-positive patients had a significantly increased risk of developing joint and tendon symptoms. Moreover, HLA-B27 positivity correlated with the development of more severe and prolonged joint symptoms.